BB2

A Round-About Way To Diagnose Cancer

Round Cell tumors are both difficult to diagnose and to explain to pet owners.

April 17, 2009

By Kevin A. Hahn, DVM, Ph.D.

One of the more confusing times in an oncology examination room is describing what a "round cell tumor" is to a pet owner.

The term is broad and describes myriad tumors that appear cytologically or histologically as a monotonous population of undifferentiated cells with high nuclear to cytoplasmic ratios.

In dogs, this group includes mesenchymal and epithelial tumors as osteosarcoma, rhabdomyosarcoma, certain melanomas, chondrosarcoma, and basal cell tumors.

However, the ultimate origin of most "round cell tumors" belongs to those cells of bone marrow-derived origin such as lymphoma, mast cell tumor, or histiocytic tumors or additionally from transmissible venereal tumors.

The clinical presentation of a round cell tumor is variable, making a definitive clinical diagnosis difficult.

However, the role of immunocytochemistry and immunohistochemistry continues to emerge as a tremendous aid in obtaining the proper diagnosis so that appropriate treatment plans and prognoses can be presented to the pet owner.

The identification of neoplastic disease relies on the microscopic features of the tumor cells and their similarity to normal cellular counterparts. So, in the case of well differentiated tumors, the cellular identity is frequently achieved. However, for the poorly differentiated tumors assigning a cell of origin becomes much more difficult.

Antibody Tests

Hundreds of antibodies are used for immunohistochemical tests by laboratories at various state and private centers. Most procedures may be performed on formalin fixed tissues; however, fresh or frozen tissue samples prepared on unstained slides may be necessary for others.

Some antibodies are quite specific, meaning that they react only with one type of cancer. Others may react with a few types of cancer, so testing with several antibodies helps to make a decision about a cancer's origin.

While not an exhaustive review of the possibilities, here are some of the filaments or antigens we rely upon our pathologists to consider when presented with a round cell tumor.

Most epithelial tissue and tumors of epithelial origin (carcinomas) stain positive for various cytokeratin filaments. Neural filaments are diagnostic of neural cells and some types of neuroendocrine tumors such as thyroid tumors and some dermal melanomas.

Vimentin is an intermediate filament that is typical of mesenchymal cells and their derived tumors such as sarcomas and other nonepithelial neoplasms. Desmin is an intermediate filament that is characteristically present in muscle cells and in most tumors derived from muscle cells.

Markers

Together, we can use vimentin and desmin to diagnose osteosarcomas, undifferentiated sarcomas and rhabdomyosarcomas.

Kappa and lambda light chains are excellent markers for detecting canine B-cell lymphomas and plasmacytomas; as are markers for cluster differentiation (CD) antigens such as CD79a (for B cells) and CD3 (for T cells). CD 18 is often used as a marker to identify all bone marrow-derived cells.

Neuron-specific enolase and S-100 protein are often present within amelanotic melanomas. The combined use of vimentin, S-100 protein and neuron-specific enolase is useful in distinguishing amelanotic melanoma from other undifferentiated round cell tumors in dogs.

Additional derivation of a round cell origin can be made through the use of smooth muscle actin, desmin, Factor VIII-related antigen and glial fibrillary acidic protein (for sarcomas) or staining for specific proteins such as various hormones and hormones receptors such as estrogen receptor.

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